reducing risk, recurrence, and treating the underlying...
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Reducing Risk, Recurrence, and Treating the Underlying Cause of Breast Cancer
Ronald L. Stram, MDStram Center for Integrative Medicine
Cancer development and progression is a complex process that involves a host of functional and genetic abnormalities
Epigenetic modification: DNA methylation, histone acetylation, genomic mutations and altered gene expression resulting in a change in overall cell function.
Cancer cells: contain full complement of bio-markers necessary for survival: proliferation, differentiation, cell death and expression of cell type function.
Cancer cells: Lack the enzyme, catalase, needed to convert H202 to 02 and H20
Cancer cell: altered regulation of cell function
Tumor initiation
requires two
genetic alterations:
losing the ability of
apoptosis; and
loss of cell to cell
contact inhibition
Tumor Initiation and Growth Disinhibition
Host Immune Response to Infection and Cancer: Unexpected Commonalities
Inflammation and Cancer
25 % of all cancers
have a known
infection or infection
associated chronic
inflammation
What are Microbes?Microbes: organisms that are too small to be seen with the naked eye
2-3 TRILLIONThe human microbiome is made up of more
than 2-3 trillion bacteria, fungi, protozoa, and
viruses that live in and inside the body
1-2X We have 1-2 times more microbial cells in our
body than human cells and the majority live in
our guts- especially the large intestine, or colon
www.serestherapeutics.com
Microbiome
Endo-Biome:
Microbiomecontrols production, inhibits or supports hormonal
balance.
Depressioninitiates production of serotonin, dopamine and
norepineprine
Polycystic ovary/ endometriosis/
Menses / Menopause/ breast cancer/
prostate cancer
produces all three estrogens : estrone, estradiol and estriol ( estriol- protective against osteoporosis
and menopause symptoms) and progesterone.
Correcting dysbiosis
may be the key for preventing or reversing estrogen related conditions
History of FMTAncient China
Oral use of human fecal material for food poisoning or severe
diarrhea
Veterinary Medicine
Transfaunation (transfer of fresh
feces) from healthy horses to treat
horses with diarrhea
rumen
transfaunation: cows
1958: Dr. Eismann
FMT enema for 4 pts with
pseudomembranous colitis (all recovered)
FMT (Fecal Microbiota Transplant)
Drug Companies and Doctors Battle Over
the Future of Fecal Transplants- March 3,2019
Dietary Interventions in Cancer Reduction
Recent research suggests that the microbiota of women
with breast cancer differs from that of healthy women,
indicating that certain bacteria may be associated with
cancer development and with different responses to
therapy.
Breast Cancer and the Microbiome
The rise in the new breast cancer cases among women
could be attributed to excess body weight. Their dietary
pattern, which correlates with obesity, can be an important
factor in the etiology of cancer.
Breast Cancer and Diet
Anti-Inflammatory DietsAm Coll Nutr. 2015;34 Suppl 1:14-21. doi: 10.1080/07315724.2015.1080105.
A diet rich in colorful, non-starchy vegetables can contribute adequate
amounts of polyphenols to help inhibit nuclear factor (NF)-κB (primary
molecular target of inflammation)
Understanding the impact of an anti-inflammatory diet on silent
inflammation can elevate the status of diet from simply a source of calories
to the cutting edge of gene-silencing technology.
Conclusions:
• Greater adherence to the Mediterranean diet has been linked to
significant reduction in overall mortality and morbidity
• microbiotia revealed lower E Coli counts and higher Bifidobacterium
• opposite results found in those following fast food consumption
• CRC (Colo Rectal Cancer) is the third most common cancer
worldwide
• Heme content in red meat is 10 times greater than that of white
meat.
• N-nitroso compounds ( NOCs) produced by bacterial
decarboxylation of amino acids and lipid peroxidation create
free radicals and increases carcinogenisis .
Free Radical Exposure and Cancer Development
• Extremely reactive if generated in the area of DNA- breaks strands
Hydroxyl Radical (0H)
• Interacts with protein and causes cell damage
Superoxide 02 interacts with Nitric Oxide ( NO)
Relationships between Oxidative Stress, Cancer Development and Therapeutic Interventions
Examples of Anti-oxidants: Flavonoids and Cancer Prevention: A Review of the EvidencePublished online, 13 Aug 2012, Authors: Donato F. Romagnolo PhD, MS & Ornella I. Selmin PhD
A Major Challenge
Dose and timing of exposure may influence the anticancer response to flavonoid-rich diets. A limited number of
intervention trials of flavonoids have documented cancer preventative effects. Proposed anticancer mechanisms for
flavonoids are: inhibition of proliferation; inflammation; invasion; metastasis; and activation of apoptosis.
Epidemiological studies suggest dietary intake of flavonoids may reduce the risk of tumors of
the breast, colon, lung, prostate, and pancreas
Vitamin C
Involved in tyrosine metabolism and is a cofactor in the synthesis of carnitine, thyroxin, norepinephrine, dopamine, and tryptophan.
Vitamin C metabolic processes includes oxidation-reduction reactions and cellular respiration, carbohydrate metabolism, synthesis of lipids and proteins, catabolism of cholesterol to bile acids, conversion of folic acid to folinicacid, and iron metabolism.
Vitamin C deficiency can cause fatigue, personality changes, and decline in psychomotor performance and motivation within 84 to 97 days.
Vitamin C is a commonly used water-soluble vitamin. Although many mammals can
produce vitamin C, humans must obtain vitamin C from foods and other sources.
Vitamin C
Hydrogen peroxide is a pro-oxidant, capable of causing free radical damage.
In normal cells, the enzyme, catalasedisables hydrogen peroxide. Thus, in normal cells, vitamin C retains its antioxidant effect.
Tumor cells, however, lack catalase, and cancers are thus vulnerable to damage from hydrogen peroxide.
Vitamin C is a commonly used water-soluble vitamin. Although many mammals can
produce vitamin C, humans must obtain vitamin C from foods and other sources.
Vitamin C
Tumor cells also selectively take up vitamin C, so they accumulate it to higher levels than normal cells, increasing their vulnerability to hydrogen peroxide.
High doses can be harmless (or even beneficial) to normal cells, but at the same time, kill tumor cells.
Furthermore, since IV C creates a pro-oxidant effect, it is unlikely to counteract the effect of chemotherapy.
Vitamin C is a commonly used water-soluble vitamin. Although many mammals can
produce vitamin C, humans must obtain vitamin C from foods and other sources.
Further Vitamin C Studies
Intravenous Vitamin C Administration
Improves Quality of Life in Breast Cancer
Patients during Chemo-/Radiotherapy and
Aftercare: Results of a Retrospective,
Multicentre, Epidemiological Cohort Study
in GermanyIn Vivo, 2011 Nov-Dec;25(6):983-90Authors: Claudia
Vollbracht, Berthold Schneider, Van Leendert, Gabrielle
Weiss, LeoAuerbach, Josef Beuth
High Doses of Vitamin C to
Improve Cancer Treatment Passes
Human Safety TrialCell Press, March 30, 2017
High-Dose Parenteral
Ascorbate Enhanced
Chemosensitivity of
Ovarian Cancer and
Reduced Toxicity Science News. Authors: Yan Ma,
Julia Chapman, Mark Levine, Kishore
Polireddy, JeanneDrisko and
Qi Chen
TurmericThe applicable part of turmeric is the rhizome. Turmeric's major active constituents are curcuminoids including curcumin (diferuloylmethane), a yellow pigment used as a food coloring
Curcumin seems to have anti-inflammatory activity, possibly by inhibiting cyclooxygenase-2 (COX-2), prostaglandins, leukotrienes, and other cytokines involved in proinflammatory signaling pathways.
Turmeric also exhibits chemopreventiveand growth inhibitory activity against several tumor cell lines. It seems to induce apoptosis in cancer cells and may inhibit angiogenesis.
Curcumin might reduce activity of procarcinogenic eicosanoids, such as prostaglandin-E2 and 5-hydroxyeicosatetraenoic acid (5-HETE), via inhibition of cyclooxygenases and 5-lipoxygenase
Turmeric
.
Preliminary evidence suggests curcumin can also reduce precancerous rectal aberrant crypt foci. Curcumin might have antithrombotic effects. Preliminary research suggests it might inhibit platelet-activating factor and arachidonic acid platelet aggregation, possibly by interfering with thromboxane synthesis.
Other preliminary research suggests that turmeric and curcumin might also have antioxidant and immunostimulatory effects.
The applicable part of turmeric is the rhizome. Turmeric's major active constituents are curcuminoids
including curcumin (diferuloylmethane), a yellow pigment used as a food coloring
Impact of Antioxidant Supplementation on Chemotherapeutic Toxicity: A Systematic Review of the Evidence from Randomized Controlled TrialsIJC International Journal of Cancer, Authors: Keith I Block, Amanda C. Koch, Mark N. Mead, Peter K. Tothy,
Robert A. Newman, Charlotte Gyllenhaal
The majority (24) of the 33 studies included reported evidence of decreased toxicities from the concurrent use of antioxidants with chemotherapy.
Only 1 study (vitamin A) reported a significant increase in toxicity in the antioxidant group.
Five studies reported the antioxidant group completed more full doses of chemotherapy or had less dose reduction than control groups.
This review provides the first systematically reviewed evidence that antioxidant supplementation during chemotherapy holds potential for reducing dose‐limiting toxicities.
Literature suggests that up to 87% of patients
with cancer take antioxidant supplements.
Hyperbaric Oxygen Therapy
Hyperbaric Oxygen Therapy (HBOT)
Cancer and Hyperbaric
Hyperbaric oxygen therapy (HBOT) is currently being utilized in conjunction with conventional treatments, including radiation and chemotherapy. Cancer thrives in hypoxic environments and HBOT has been shown to increase these oxygen levels to weaken tumors and reduce their aggressiveness. Studies have demonstrated the benefits of HBOT for cancer with the following:
Enhance “Conventional” Cancer Therapies and Treatments with HBOT
• Reduce Tumor Hypoxia
• Better Radiation Therapy Results
• Improves Chemotherapy Outcome
• Enhances Brain Treatment
• Decreases Tumor Drug Resistance
• Allows for Optimal Therapy Dosage to be Attained
• Increases Post-Op Fibroblast Activation
Reduce Side Effects of “Conventional” Cancer Therapies and Treatment with
HBOT
• Reduces Radiation Therapy Side Effects
• Decreases Chemotherapy Side Effects
• Accelerates Post-Operative Healing & Prevents Infection
• Reduces Chemo-Brain Syndrome Symptoms
Enhance IV Cancer Treatments with HBOT• Increase Intravenous Vitamin C Therapy Effects
• Enhance Chemotherapy Uptake
Reduce Tumor Aggressiveness with HBOT• Weakens Hypoxic Tumors
• Targets Metastatic Tumors
Increase Natural Killer Cell Activity with HBOT• Increase Oxy-Radical Production
• Amplifies Apoptosis Effect
Acupuncture
Acupuncture
Acupuncture for Cancer-Related Fatigue in Patients With Breast Cancer: A Pragmatic Randomized Controlled Trial Journal of Clinical Oncol 30:4470-4476 Alexander Molassiotis, Joy Bardy, et al.
Acupuncture is an effective intervention for managing the
symptom of cancer related fatigue and improving patients’ quality of life
Electroacupuncture has demonstrated benefit for chemotherapy-induced
acute vomiting
Acupuncture-Point Stimulation for
Chemotherapy-Induced Nausea
and VomitingCochrane Database Syst. Rev. 2006 Apr 19, Ezzo
JM1, Richardson MA, Vickers A, Allen C, et al.
Real-Life Application
Case Presentation
• Patient was tested in early twenties as part of a research study. Patient + BRCA 2.
• October 2005- DCIS- s/p right breast lumpectomy s/p radiation-completed 6 weeks.
• July 2015- had mammogram- patient developed lump in left breast and chose to have a double mastectomy with implants . All biopsies have been ER +. No chemotherapy or radiation at this time. Patient reports she has never had hormone therapy.
• August 2018- patient saw PCP and had blood work and was called immediately and advised to go to the hospital. Patient reports "something about a C-protein and concern for infection and anemia". Patient also had a chest x-ray that also made PCP concerned. Patient was told she had stage IV metastatic breast cancer to bones (spine, pelvis, sternum and ribs). Patient reports blood count was 9.0 and her recent blood work revealed 7.8.
Most prominent symptom:
• Generalized painIntensity: 7/10 (10=worst), it can go down to 3/10Frequency: Daily
• Ambulating with a walker because it makes her more comfortable.
Symptoms
Images Representing Metastasis
Treatment Plan
• Melatonin
• Collagen Peptides
• Methyl Factors
• Iron Bisglycinate
• MRS Mushroom Formula
• Turkey Tail
• ProEPA
• Turmeric
Supplements
• Acupuncture
• IV Vitamin C 50 g 2x per week
• Hyperbaric Oxygen with a total of 40 sessions
Adjunct Therapy
Questions